Purpose:

Some studies suggest a window of opportunity for the treatment of rheumatoid arthritis (RA) to regain normal physical functioning.1 The relationship between RA disease severity and ability to regain normal function during treatment has not yet been studied. We evaluated the effect of combination therapy with adalimumab and methotrexate (ADA+MTX) on physical function of patients who have moderate or severe disease and either early or long-standing disease.

Methods:

Observed data were analyzed from patients who received combination treatment with ADA+MTX in 2 long-term clinical trials: DE019 (5 years of treatment for long-standing RA) and PREMIER (2 years of treatment for early RA). Patients were categorized by baseline disease activity as either moderate (3.2<28-joint Disease Activity Score [DAS28]<=5.1) or severe (DAS28>5.1). Mean Health Assessment Questionnaire (HAQ) scores for each group of patients were calculated at baseline, 6 months, 1 year, and 25 years. Improvements in physical function were evaluated through 2 different standards: HAQ<=0.49 for the normal population and HAQ<=1.2 for the RA population.

Results:

In the long-standing RA population (DE019), patients with moderate disease achieved a 59% reduction of HAQ to a mean of 0.45, which was within the range for the normal population; this improvement was maintained over the 5-year study period. Patients with severe disease improved 43% to a mean of 0.88, which was within the range of normal functioning for RA patients but not for the normal population. By 1 year, >60% of patients with moderate disease but only 34% of patients with severe disease achieved normal population HAQ scores; this difference was maintained over 5 years. In the early RA population (PREMIER), patients with both moderate and severe disease at baseline regained physical functioning to within the range of the normal population at 1 year; patients with moderate disease had a 73% reduction in HAQ to a mean of 0.25, and patients with severe disease had a 71% reduction in HAQ to a mean of 0.44. At 1 year, 70% of patients in the moderate group and 61% of patients in the severe group reached normal functioning.

Conclusion:

In both early and long-standing RA, patients with moderate disease who receive combination therapy have a great likelihood of achieving normal physical function. In contrast, for patients with severe disease, the efficacy of combination therapy is greater in the early RA group, suggesting that a window of opportunity for preventing irreversible functional loss exists in patients with highly active disease.